BMH Medical Journal

BMH Med. J. 2020; 7(Suppl): Early Online. Geriatrics & Gerontology Initiative: International Workshop on Care of the Elderly

Clinical Consequences of Aging

Introduction

The healthy older person has several distinct recognizable clinical attributes. However, many of the effects of ageing occur without overt manifestations. The combined effect of age-related changes gives rise to new syndromes, and alters the signs and symptoms of well known diseases. this makes caring for the elderly a complex clinical exercise. Knowledge of the patho-physiology of ageing enables the clinician to appreciate these differences and aids in early and accurate diagnosis.

There are many theories of aging, but they are incompletely understood. Most gerontologists agree that genetic factors, coupled with environmental influences, drive cellular degenerative changes. These factors are so varied that the speed and type of ageing is highly diverse hence the elderly are a heterogenous group, with no two individuals having the same ageing “phenotype”.

Primary ageing is inevitable and the term describes the well- known phenotype of the aged person, characterized by greying and/or loss of hair, decrease muscle and bone mass, arteriosclerosis, menopause, decreased taste, vision and hearing, impaired immunity, and impaired renal function, among other changes. The degenerative changes are related to the concept of the “biological clock”, a term used to denote that a cell is genetically programmed to undergo a fixed number of cell divisions each one resulting in telomere damage. This telomeric damage finally causes unravelling of the chromosomes, leading to cellular death. Other causes of cellular death include damage by oxygen free radicals, and mutations. Primary aging is accelerated by chronic diseases such as diabetes and hypertension and their sequelae. Environmental toxins which include alcohol, smoking and substance abuse also contribute. This has been described as “secondary aging”.

The sudden pre-terminal decline in functionality, due to acute infection, stroke or a myocardial infarction is termed as “tertiary aging”. The latter causes a precipitous, usually non-reversible, decline in functional status, or death.

While primary aging is inevitable, and therefore not amenable to intervention (nor should there be an attempt to do so), the secondary and tertiary stages of ageing are areas where the society and medical profession have much to recognize and ameliorate. The purpose of clinical interventions is not to achieve “immortality” but to promote healthy aging and to relegate the morbidity of aging to the terminal tertiary stage. This has been termed as “compression of misery”.

The pace of ageing is very variable in individuals, hence chronological age and biological age diverge significantly. Some people at 90 years may be able to function well independently due to healthy aging, whereas some persons in their sixties, may undergo premature aging, resulting in a life of dependence for all activities of daily living.

“Homeostenosis” is a word coined to denote the inability of aged persons to adapt to stress because of a loss of reserve function in each organ system. In general, an otherwise healthy elderly person should be able to function normally at rest. However, under physical stress the organs are unable to reach the maximal response possible at younger ages. In addition, the return to normal basal levels post exercise is delayed. Similarly, challenges to metabolic stress such as dehydration, dyselectrolytemia, or hyper- or hypoglycaemia, are poorly tolerated due to inefficient counter-regulatory processes. The ability to maintain the “milieu interior”, homeostasis, is affected.

A brief overview of the age-related changes is some of the organ systems is described below.

Isolated systolic hypertension is very common, and contributes to stroke and coronary and renal disease. Postural hypotension is also prevalent and should be looked for in all elderly when seen for the first time, and specially when there are complaints of dizziness and syncope. One should use caution when using antihypertensive therapy because the diastolic pressure should not be lowered below 60 mm Hg, as this will lower tissue perfusion. A rare manifestation of age-related arteriosclerosis is “pseudo-hypertension”. This refers to spuriously high blood pressure which does not seem to respond to treatment. This is because of thickened brachial artery which does not get compressed by the inflated BP cuff, and hence the first Korotkoff sound is erroneously heard at an elevated level, and there appears to be no response to increasing doses of anti-hypertensive medications.

Failure of relaxation of the hypertrophied left ventricle in diastole results in increase in left atrial pressure leading to elevated pulmonary capillary pressure and pulmonary edema. This type of heart failure due to diastolic dysfunction is missed if one relies only on ejection fraction (EF) on echocardiography. Heart failure with preserved ejection fraction (HFpEF), or left ventricular diastolic dysfunction, is the terminology given to this type of heart failure. HFpEF is recognized by the changes in E/A (early filling/ atrial filling) ratio.

Central Nervous System

Decrease in brain volume is consistently noted on brain imaging. Cerebral atrophy involves both grey and white matter, with compensatory expansion of the ventricular system. Grey matter loss occurs predominantly in the prefrontal cortex, striatum, temporal lobes especially in the hippocampus and amygdala. There is loss of dendritic arborization resulting in less synapses, decreased neuroplasticity and decrease in some neuro transmitters (dopamine, serotonin & acetyl-choline). There is deposition of beta amyloid protein and amyloid precursor protein. White matter loss is predominantly in the frontal cortex.

Cognitive decline is inevitable with the changes described above. In addition, the altered balance of neuro-transmitters, particularly the decrease in acetylcholine, results in an increased vulnerability to developing reversible confusion and disorientation when stressed by disease or drugs. Delirium is the term most used to describe this state. Depression is also a common old age problem, often difficult to diagnose because it may manifest as memory loss.

The typical memory disturbance experienced by healthy elderly does not interfere with normal life, and is mainly in the short-term memory domain as described below:

a) Delayed free recall, (remembering a shopping list or name of a recent film, or where one left the keys). Usually, when given a cue these can be recalled.
b) Prospective memory is also affected, so for future actions, people need reminders to take medicines or attend events.
c) Executive function is largely unaffected, but is delayed when the person is distracted or under stress. This function allows a person to organize, plan, problem solving, and make judgements.

Abnormal types of memory loss in the elderly:A more advanced form of memory loss is known as mild cognitive impairment (MCI). Though the person with MCI can continue functioning normally as far as activities of daily living are concerned, he/she has difficulty in tasks involving executive function. For example, the person may need help with financial transactions, organizing a meal, or comprehending the newspaper. Family members usually notice lack of initiative, disorganization, and the patient’s fear that his/her memory is declining. Patients with MCI may have a 15% risk per year, of progression to dementia. Tests of memory function are usually normal or borderline and need to be repeated every 6 months. The most severe form of memory loss is Dementia. Dementia is a disease, and the prevalence increases with age. There are many forms of dementia, the commonest being Alzheimers type. The memory loss is so severe that the person is unable to perform daily living activities such as toileting, dressing and eating, and is unable to recognize family members.

Insomnia is a common symptom in the elderly. Insomnia may be due to drugs, nocturia, dyspnoea or pain. Even in the absence of these factors, sleep disturbance is common, and attributed to hypothalamic dysfunction and melatonin dysregulation. Patients usually demand sedatives which are prescribed extensively by their physicians. Sedatives are in fact detrimental to older people as they are implicated in falls, cognitive decline, and worse, are addictive. Therefore, doctors should be very cautious and always attempt non-pharmacological means to improve sleep hygiene.

Kidneys: There is a decrease in renal volume after the age of 50 years predominantly due to global glomerular sclerosis consequent to reduced renal blood flow due to arteriosclerosis. As a result of this there is a decline in glomerular filtration rate (GFR), at the rate of 0.7 to 0.9ml/kg/min for every year after the age of 40 years. At 20 years of age the mean GFR is around 100-110 ml/kg/min, and declines after age 40 years to approximately 60ml/kg/min at age of 75 years.

The aging kidney is very vulnerable to dehydration, is unable to excrete a water load, and is very susceptible to damage from drugs, and toxins. Aminoglycosides, and NSAIDS should be avoided. The combination of diuretics and NSAIDS is specially harmful. NSAIDS prevent prostaglandins from maintaining intrarenal vaso-dilatation, specially in the presence of diuretics and dehydrated state. It is a good practice to adjust dosing of most drugs in the elderly according to estimated GFR.

Incontinence: The detrusor muscle, innervated by the parasympathetic nerves, contracts under the influence of the pontine micturition centres (PMC), which are under tonic inhibition from the prefrontal cortex. This inhibition is decreased as the person ages, leading to bladder contractions at small volumes, also termed as detrusor overactivity. This sensation becomes difficult to disregard, making the older person unable to delay voiding at inconvenient times such as during traveling, or at a concert. This is known as urgency, and can result in incontinence. Anti-muscarinic drugs are available to reduce this symptom. Another cause of incontinence in the male is outflow obstruction due to prostatic hypertrophy. Retention of significant amounts of urine post- voiding leads to infection, and overflow incontinence. Stress incontinence is common in the female, who due to child-bearing, may have a lax pelvic floor. Small volumes of urine can leak during coughing or straining. The doctors’ role is to identify, and treat, incontinence in the older person. Most forms of incontinence can be ameliorated, if identified and evaluated.

Nocturia (passage of urine more than once after going to bed) is a common complaint, and can be troublesome, causing sleep fragmentation, falls, and incontinence. Often the problem is exacerbated by infection, prostatic hypertrophy, or drugs which need to be identified. Despite a thorough evaluation, however, some people have a purely age-related nocturia. This has been ascribed to detrusor overactivity, as described above, and decreased urinary bladder capacity and compliance. Other metabolic changes such as increased nocturnal sodium excretion, catecholamines, and BNP (brain naturetic peptide), are responsible for increased nocturnal urine volume, contributing to nocturia. Understanding of these factors has led to the use of desmopressin (ADH analogue) as an effective treatment for age-related nocturia in selected cases.

Osteoporosis is predominantly a problem among women as the sudden cessation of estrogen production at the menopause accelerates bone loss. This process is slower in the male due to a more gradual reduction in androgen secretion which can continue till the seventh decade. While hormone replacement therapy was used in the past to counteract osteoporosis in women, it is no longer advocated due to adverse cardiovascular effects. Instead, regular screening of bone mineral density is advocated after the age of 65 years. If osteoporosis is discovered then pharmacological agents such as bisphosphonates are recommended. Supplementation of Vitamin D, and a diet rich in calcium has been shown to diminish bone resorption and retard osteoporosis, and is advised in all women at menopause.

Osteoarthritis of the weight-bearing joints, such as the hips and knees and low back, is common, and should be addressed early on with physiotherapy, walking aids, and prudent analgesic regimen. Opioids and NSAIDS cause harm, and should be avoided. Thus use of paracetamol is the only safe drug option, with limited NSAID use under close supervision to prevent renal and gastro-intestinal side effects.

Frailty: Some elderly experience unexplained weight loss, poor muscle strength, loss of energy, slow walking speed, low physical activity, and decreased grip strength. This has been termed as the “frailty syndrome”. The pathogenesis of frailty is under active research and currently chronic inflammation, poor nutrition and genetic predisposition are thought to be causal factors. Frailty is a risk factor for falls and death.

Poor dentition, and loss of taste and thirst sensation, are common in the elderly and can contribute to poor nutrition and dehydration. Oesophageal dysfunction results in tertiary contractions super-imposed on the usual normal propulsive contractions, and can give rise to dysphagia and to angina-like chest pain.

The rest of the gastro-intestinal tract, and absorption of nutrients is not greatly affected. Though changes in colon transit time have been noted, there are no specific age-related changes to account for the common complaint of constipation in older persons. Constipation is a difficult clinical problem in frail individuals with poor mobility, decreased water intake; diabetes, hypertension and stroke, medications, worsen constipation and result in faecal impaction.

Liver functions are generally normal, including it’s capacity to biotransform drugs. Albumin production is decreased leading to changes in drug binding in those drugs which are highly protein-bound. The function of first-pass metabolism is decreased affecting the blood levels of some drugs such as beta-blockers.

Hypoglycemia: Ageing leads to decreased ability to tolerate hypoglycaemia, due to impaired counter-regulatory responses. It is a serious complication of anti-diabetic therapy, leading to falls and death, and should be judiciously avoided, even at the expense of inadequate control of diabetes.

Hyponatremia: This is a common disturbance in the older person when stressed by disease states. In the absence of overt dehydration and volume loss, hyponatremia is mainly due to inappropriately elevated levels of anti-diuretic hormone. This also causes an impaired ability to deal with an increased water load. Complex physiological changes in the renal tubules with regard to modification of urine concentration contribute to this. This knowledge has prompted the use of ADH analogues such as tolvaptan. This is used extensively to correct recalcitrant hyponatremia and the fluid overload of heart failure. Thus one cannot advise all elderly patients to consume large quantities of fluids; on the other hand they should be advised to drink sufficient liquids consciously, especially in hot and humid conditions, because of the decreased thirst sensation.

Endocrine functions are affected with ageing. Apart from decline in ovarian and testicular function, hypothyroidism is a common occurrence in the elderly. On the other hand, over- treatment of sub-clinical hypothyroidism is harmful and can lead to osteoporosis and atrial fibrillation. The widespread use of the drug amiodarone for cardiac arrhythmias has resulted in iatrogenic thyroid disease which requires therapy.

Normal aging is associated with increased thoracic kyphosis, with increase in intra-thoracic volume, leading to elevated residual lung volume, and decreased elastic recoil. There is a reduction in vital capacity. These changes are termed senile emphysema, and can exacerbate the dysfunction of super-imposed diseases such as obstructive airways diseases. There is an increased vulnerability to respiratory infections, due to a decreased clearance of secretions by the muco-ciliary apparatus, as well as aspiration of oro-pharyngeal secretions.

The epidermis, and dermis undergo thinning. There is loss of fat, collagen and elastic tissue resulting in wrinkles, and loss of moisture, though sweating and sebum production remain intact. Senile purpura occurs with minor injuries. Itching in the absence of disease is a difficult symptom to control. Decubitus ulcers are common in bed bound elderly.

"Immunosenescence" is a term used to describe decline in immune function due to ageing. Many factors are responsible for poor immunity, namely B cell dysfunction and an altered CD4/CD6 ratio; neutrophil function is impaired; and interleukin 6 secretion is increased. Not only does this result in increased susceptibility to infections, and a reduced response to vaccination, but also organ damage due to increased inflammation. “Inflammaging” is a term coined to describe the role of inflammation in the patho-physiology of chronic diseases such as cardiovascular disease, frailty and cerebrovascular diseases.

Presbyopia, or long-sightedness starts by age 40 years as a result of lenticular changes. Cataracts are not inevitable but are more common in diabetics. Decrease in lachrymal secretion causes dry eyes and the symptom of unexplained irritation. Vision can be severely compromised due to open angle glaucoma, age-related macular degeneration and diabetic retinopathy. The visual loss is very gradual and often ignored, hence all elderly, especially diabetics, should have annual eye check.

Hearing loss is also very common and can be of conductive or sensori-neural type, the latter is more common and has a genetic predisposition. Taste and smell sensation are affected frequently and result in poor food intake. There is a tendency to supplement sugar and salt to enhance taste, leading to deterioration of co-morbid diseases.

The deterioration of organ systems, as briefly described above, gives rise to several clinical problems, or geriatric syndromes, which are peculiar to the elderly. These need to be diligently identified, even if the patient has no complaints. This is the basis of the CGA (comprehensive geriatric assessment) which must be performed in all elderly in order to identify occult dysfunction, and potential sources of morbidity.

The common geriatric syndromes are:

1. Falls
2. Urinary incontinence
3. Fragility fractures
4. Heart failure
5. Hypertension
6. Delirium, dementia, depression
7. Frailty
8. Stool impaction
9. Iatrogenesis due to polypharmacy
10. Insomnia
11. Infection
12. Impaired hearing and vision

The above description of changes in the various organ systems is universal. However, the extent of change varies from person to person. So while one person may have more severe neurological and cardiovascular changes, the renal and musculoskeletal ageing may be less pronounced, and vice versa. This highlights the fact that each older person is unique, and has a “weak link” in the function of the “chain” of organ systems. When the older person develops a disease, eg. an infection, or a side effect of a drug, the organ which is most “aged”, the “weak link” , is the one that presents symptoms; this point is understood by the adage “a chain is no stronger than it’s weakest link”. For example, a respiratory tract infection, may present as delirium in a person with a more aged brain, while a person with more musculoskeletal changes will probably manifest this as a fall. This set of stereotypical presentations of disease based on the “weak link” concept is termed as the “Geriatric Giants” .

So, if an elderly person suddenly becomes confused, incoherent, or apathetic, he or she is not necessarily having a stroke or a psychiatric disturbance, but could have a urinary or respiratory infection, or dyselectrolytemia etc. Similarly, a fall may cause a hip fracture, so while the fracture is being “fixed”, it is important to detect the cause of the fall and prevent it’s recurrence.

Given the extent and variability of organ degeneration it is essential that the elderly need periodic comprehensive clinical assessments, and the results of these must drive a multi-disciplinary approach to holistic care. The allied health disciplines, which would usually include physiotherapists, geriatric nurses, social workers, pharmacists, and dieticians, mental health therapists, are necessary to deliver this care.

The philosophy of caring for the elderly focuses on maintenance of functionality, rather than cure, because aging cannot be reversed, though the pace can be slowed. The care teams’ approach is to make as many small improvements as possible in each area, because this leads to significant overall enhancement of quality of life.

Aging is a complex process of variable pace and complexity creating a divergence between chronological and biological age. The changes in different organs result in morbidities which are peculiar to the elderly, known as the geriatric syndromes. The age-related changes also modify the presentation of diseases, giving rise to the “Geriatric Giants”. These act as red herrings, diverting clinical suspicion away from the actual diagnosis.